FDA Clears One-Time Gene Shot to Halt Sanfilippo's Rapid Decline

One-time infusions of a new gene therapy now carry a price tag of nearly $4 million, a cost that ties the drug for the second most expensive ever recorded by the research firm 46brooklyn. The treatment, approved by the Food and Drug Administration in September, is designed for children with Sanfilippo syndrome, a rare inherited disorder that leads to severe developmental decline.

The path to this approval began in 2013 when Eliza O'Neill, then three years old, was diagnosed in Columbia, South Carolina. Her mother, Cara O'Neill, a pediatrician, noted that Eliza had a pragmatic speech delay, meaning she knew many words but could not use them in typical social contexts. A colleague suggested testing for metabolic disorders, and the results confirmed Sanfilippo. The condition stems from a faulty gene that prevents the body from breaking down heparin sulfate, a molecule essential for normal cell function.

As the molecule builds up, children lose the ability to speak and walk and often experience seizures. The Cure Sanfilippo Foundation, which the O'Neill family started and runs, states that patients usually do not live past their teenage years. Glenn O'Neill, Eliza's father, described the immediate realization of the disease's rapid progression. He recalled that upon returning home after receiving the test results, he understood the urgency. The family decided they needed to act immediately to find a treatment.

Researcher Haiyan Fu at Nationwide Children's Hospital in Columbus, Ohio, had been developing a gene therapy for Sanfilippo in mice since the late 1990s. The approach uses a modified virus to deliver a working copy of the broken gene to patients' cells. Fu believed that early treatment could potentially cure the condition. However, funding remained a persistent challenge. In 2009, Fu considered quitting but was encouraged to continue by families of affected children who had supported her work from the start.

Eight patient foundations, including Ben's Dream and a Cure for Kirby, helped keep the research alive until it was ready for human trials. To fund the first clinical trial, Glenn O'Neill reached out to filmmaker Benjamin Von Wong in 2014 to create a viral video about Eliza's story. The resulting video, titled Saving Eliza, helped the family break the GoFundMe record at the time. They raised one million dollars in a few weeks, eventually reaching two million dollars. This funding supported the trial that began in May 2016, with Eliza becoming the first patient.

The promising results attracted the attention of the biotech industry. In 2022, Ultragenyx acquired the rights to the gene therapy and continued its study. The company later submitted data to the FDA for review. Emil Kakkis, the CEO of Ultragenyx, noted that the treatment works best in younger children because more brain tissue remains intact. He explained that children treated at six months have shown strong results, whereas those diagnosed at two or three years old have already lost developmental ground.

Kakkis stated that the company is committed to treating every patient regardless of cost. He said there should be no logistical, site, or state rule that prevents a patient from receiving the therapy. The FDA approved the drug, named Fayuvi, in September. Shortly after the announcement, Fu received a call from Cara O'Neill and messages from other families who had funded the research. Some of those families had lost children during the lengthy development process.

Fu described the approval as good news but noted mixed emotions, stating it should not have taken this long. Eliza is now almost 17 years old. She was treated with the gene therapy at age six, by which time she had lost her ability to speak. The ability to speak did not return, but she now communicates using picture cards and devices. She attends school and spent the summer swimming and learning to float on a pool noodle. Glenn O'Neill expressed pride in his daughter, acknowledging the difficult journey while noting that she is lucky.

The approval marks the end of a decade-long effort that began with a single family's determination to find a cure. The cost of the treatment reflects the complexity of the research and the high stakes of the clinical trials. The drug is now available for use in the United States, offering a new option for families facing this rare diagnosis.